تقرير
Disruption of the mitochondrial network in a mouse model of Huntington's disease visualized by in tissue multiscale 3D electron microscopy
| العنوان: | Disruption of the mitochondrial network in a mouse model of Huntington's disease visualized by in tissue multiscale 3D electron microscopy |
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| المؤلفون: | Solana, Eva Martin, Zueras, Laura Casado, Torres, Teobaldo E., Goya, Gerardo F., Fernandez, Maria Rosario Fernandez, Fernandez, Jose Jesus |
| المصدر: | Acta neuropathol commun 12, 88 (2024) |
| سنة النشر: | 2024 |
| المجموعة: | Condensed Matter Quantitative Biology |
| مصطلحات موضوعية: | Quantitative Biology - Subcellular Processes, Condensed Matter - Soft Condensed Matter, I.5.1 |
| الوصف: | Huntington's disease (HD) is an inherited neurodegenerative disorder caused by an expanded CAG repeat in the coding sequence of the huntingtin protein. Initially, it predominantly affects medium-sized spiny neurons (MSSNs) of the corpus striatum. No effective treatment is available, thus urging the identification of potential therapeutic targets. While evidence of mitochondrial structural alterations in HD exists, previous studies mainly employed 2D approaches and were performed outside the strictly native brain context. In this study, we adopted a novel multiscale approach to conduct a comprehensive 3D in situ structural analysis of mitochondrial disturbances in a mouse model of HD. We investigated MSSNs within brain tissue under optimal structural conditions utilizing state-of-the-art 3D imaging technologies, specifically FIB/SEM for the complete imaging of neuronal somas and Electron Tomography for detailed morphological examination and image processing-based quantitative analysis. Our findings suggest a disruption of the mitochondrial network towards fragmentation in HD. The network of interlaced, slim, and long mitochondria observed in healthy conditions transforms into isolated, swollen, and short entities, with internal cristae disorganization, cavities, and abnormally large matrix granules. Comment: 31 pages 5 figures |
| نوع الوثيقة: | Working Paper |
| DOI: | 10.1186/s40478-024-01802-2 |
| URL الوصول: | http://arxiv.org/abs/2406.16977 |
| رقم الأكسشن: | edsarx.2406.16977 |
| قاعدة البيانات: | arXiv |
| DOI: | 10.1186/s40478-024-01802-2 |
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